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Scientists Discover New Category of Small RNAs

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Researchers at Cold Spring Harbor Laboratory have detected a new class of small RNAs. The scientists, who are part of the ENCODE project, also say that their discovery suggests the presence of a strikingly novel biochemical pathway for RNA processing in which these and possibly other small RNAs are produced.

The team has been tasked with cataloguing the entire long and short RNA output of cells. They selected new types of small RNAs for further analysis and recently found one abundant type arising specifically from transcription start sites of gene regions also known as promoters, where the synthesis of protein-coding RNA molecules begins.

These promoter-associated small RNAs (PASRs) are different from the small RNAs found in the current research and are thus called non-PASRs. Non-PASRs are derived from different areas than from where PASRs are generated, according to the scientists. However both groups of small RNAs have undergone the process of capping, a chemical procedure that makes them stable and resistant to degradation. “This quality lengthens their lifespan in the cell, a clue that suggests these small RNA classes may have significant biological duties,” says Gregory Hannon, Ph.D.

PASRs and non-PASRs may not be initially synthesized in their short form. The investigators propose a model in which mature long RNAs are cleaved followed by a capping of the newly generated long RNA fragment. This is followed by the clipping of the end of the capped long RNA to produce a short RNA product.

Using a human gene called MYC as a model, the team studied how the presence of PASRs at the start site of a gene impacted its expression. The group found that if the level of expression of PASRs was increased, the expression of the MYC gene was reduced. Therefore PASRs seem to modulate the production of mature RNA transcripts.

But the function of the new non-PASRs is unclear at the moment. This class of RNAs “could possibly participate more globally in a bookkeeping or quality-control mechanism by which the cell keeps track of the genes it is expressing—its transcriptional output,” according to Thomas Gingeras, Ph.D., a leader of ENCODE.

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